Hydantoins containing basic



' chlorates.

Patented Oct. 28, 1952 HYDANTGINS: CONTAINING; BASIC SUBSTITIJENTS Walther Pei-sch, Frankfort-on-thc-Main-Hoch t; and Adolf P. C. Schmidt; Frankfort'-'on-the-' Main-Fechenheim, Germany, assignors to Gass'ella Farbwerke Mainkur, Frankfort-on-the- Main-Fechenheim, Germany Np Drawing. Application November 15, 1949, Serial No. 127,508

1' Our present invention relates to hydantoins containing basic 's'ubstituents.

These new compounds correspond to thegeneral formula:

wherein R1 means a bivalent radical containing alkyl groups which may be interrupted by oxygen and may be partially replaced by a phenylene group, R2 means alkyl or phenyl, R3 and R4 mean alkyl groups, and wherein R1+Rz and/or R3+R4 may be connected to form a ring.

They are obtainable by the known processes for forming hydantoin rings, when a starting material containing basic substituents is used. They may be purified as sodium salts or as per- If several isomeric compounds are obtained, these isomers may be separated as hydrochlorides or, on account of the difierence of their solubilities, in alcohol.

Our new compounds are all well soluble in alcohol, some of them in water too. Owing to the basic substituents, the acidic character of the hydantoin ring is weakened in these compounds. Their solutions show, therefore, a reaction nearer to the neutral point than the known hydantoins. In consequence of this reaction and of the radicals contained in the new compounds, they show a therapeutic action rendering them useful as medicines themselves or as intermediates for preparing other medicines.

The following examples and the table illustrate the invention more particularly, but they are not intended to limit the invention thereto; the parts are given by weight:

Example 1 96 parts of l-N-piperidino-3-oxo-butane hydrochloride are dissolved in 120 com. alcohol and mixed with 34 parts of potash, 38 parts of potassium cyanide, 110 parts of ammonium bicarbonate and 350 parts of water. The mass is stirred in a closed vessel at 65-80 C. under a carbon dioxide pressure of 14-16 atmospheres for about 8 hours. Then the vessel is opened, and the crystals found therein are separated from the mother liquor by'suction. When the liquid is concentrated in vacuo under carbon dioxide, a further quantity of crystals precipitates. All these crystals are recrystallized from methanol. The pure product represents -[2'- 1 Claim. (-01. 260-3095) 2 piperidinoethyl]-5-methyl hydantoin or the formula:

It melts at 202-203 C., and its solubility in water at room temperature is 3.4

Example 2 54 parts of 1-N-piperidino-3-oxo-4-dimethy1-- pentane is dissolved in 250 parts of alcohol and mixed with 35 parts of potassium cyanide, '70 parts of ammonium carbonate and 250 parts of water. The mass is stirred at 50-55 C. under a reflux condenser and gradually heated to boiling, until after about 8 hours the evolution of carbon dioxide ceases. By further processing the reaction mass as described in Example 1, the 5- [2 -piperidino-ethyl] -5-tert.butyl-hydant0in of the formula:

CHs-CH:

O C-NH is obtained. It represents, when recrystallized from methanol, colorless needles melting at 246.5-247.5 C. Its solubility in water at 20 C. is 0.43%.

Example 3 58 parts of l-dimethylamino-3-oxo-butane, 200 parts of alcohol, 38 parts of potassium cyanide, 100 parts of ammonium carbonate and 350 parts of water are heated in an autoclave under carbon dioxide pressure of 18-24 atmospheres to TO- C. for 11 hours. Then the mass is processed as described in Example 1. In this way 5(2'-dimethylaminoethyl) -5-methylhydantoin of the formula HN-CO CHr-CHz-N-CH:

\ (IJH a OC-NH CHa is obtained which melts when recrystallized from methanol at l81-182 C. Its solubility in Water at room temperature is 15.5%.

In the followin table some more representa- 3 tives of the compounds of our invention are named:

Melting Solubility No. Name of the compound point, in water C at 20 C Percent 1a 5-(B-dimethylamino-isopropyl) -5- 194 2v 6 ethylhydantoin. 1b, fi-(fl-dimethylamino-isopropyD-S- 153-156 13 ethylhydantoinfisomer) 2 fi-o-(B-diethylaminoethoxy- 195 0.16

phenyl) -5-ethylhydantoin. 3 5-o-(piperidinomethyD-eyclo- 204-206 0.41

hexylhydzmtoin. 4a 5-(5-piperidino-isopropyl)-5- 234-235 0.42

methylhyd entoin 4b.... 5-(fi-piperidino-isopropyl)-5- 196-198 1.58

methylhydantoin (isomer). 5. 5-o-(diethylaminomethyl) -cyc1o- 189-190 1 hexylhydantoin 6 fi-(fi-piperidino-ethyl)-5-allyl- 177-178 1.25

methylhydantoin. 7 fi-phenyl-fi-(B-piperidino-ethyl)- 189 0.29

hydantoin. 8." fi-p-(fi-diethylamino -e thoxy- 167-169. 5 0. 19

phenyl)-5-me15hyl-hydantoin. 9-.. 5-p-(fi-diethylamino-ethoxy- 162. 5-163 0.63

phenyl) -5-ethyl-hydantoin. 10,... fi-p-(fl-diethylamino-ethoxy- 153-154 0.19

phenyl) -5-propyl-hydantoin. 11 fi-o-(fi-diethylamino-ethoxy- 181. 5-1825 0. 34

phenyl) -5-methyl-hyd antoi.n. 12 S-o-(B-diethylamino-ethoxy- 156 0.096

phenyl) -5-propyl-hydantoin.

We cla1m:

4 As new compounds the hydantoins containing basic substituents and correspondingto the general formula:

wherein R means a lower alkyl group, these compounds being colorless substances having definite melting points and being well soluble in alcohol.

WALTHER PERSCH. ADOLF P. CH. SCHMIDT.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Henze et al.: Jr. Am. Chem. Soc., vol. 63, DD. 1943-1945 (1941).

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